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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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Research Article

2D QSAR Modelling, Docking, Synthesis and Evaluation of 2-substituted Benzimidazole Derivatives as Anti-breast Cancer Agents

Author(s): Remya Ramachandran Surajambika*, Barath Ramesh, Ruban Ramesh and Jaitharasan Venkatesan

Volume 20, Issue 5, 2024

Published on: 11 October, 2023

Article ID: e111023222069 Pages: 16

DOI: 10.2174/0115734072255749230928060834

Price: $65

Abstract

Background: Cancer is a leading cause of death worldwide and is anticipated to reach 28,4 million fresh cases globally by 2040. Despite all the progress made in cancer prevention, diagnosis, and treatment, mortality by cancer is in second place.

Objectives: The design of novel 2-substituted benzimidazole modelled by QSAR study. Molecular docking studies on the novel derivatives and synthesis characterization and evaluation of the anticancer activity of the novel derivatives against breast cancer cell line MCF 7.

Methods: We designed 10 novel benzimidazole derivatives modeled by 2D QSAR. From the ten compounds by applying in silico tools of ADME properties and toxicity and through molecular docking on Tyrosine Kinase (PDB ID: 2SRC). Compound 2AD showed the highest dock score of -9.5 kcal/mol followed by 2 BD and 2GD (-9.3 kcal/mol) Molecular dynamic simulation studies were conducted using CABSflex an online molecular dynamic simulation tool. Six compounds were selected for synthesis. The synthesized compounds were characterized and the invitro pharmacological activity was tested on MCF-7 cell line by MTT assay.

Results: The compounds 2AD and 2GD showed good percentage inhibition on MCF-7 cell line with IC50 values of 2.757 μg/ml and 2.875 μg/ml respectively.

Conclusion: The novel 2-substituted benzimidazole derivatives are good lead compounds for cancer therapy. Optimization of these compounds will be providing more target-specific anticancer agents.

Graphical Abstract

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